Evaluation of enzyme-linked immunosorbent assay and reversed passive hemagglutination for detection of Crimean-Congo hemorrhagic fever virus antigen

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Abstract
Enzyme-linked immunosorbent assay (ELISA) and a reversed passive hemagglutination (RPHA) test were evaluated for rapid detection of Crimean-Congo hemorrhagic fever (CCHF) virus antigens. Both RPHA and ELISA detected CCHF antigen in the brains of infant mice 2 to 3 days after infection, several days before the animals sickened and died. Antigen was also detected after 1 to 2 days in infected cell culture extracts and after 2 to 4 days in culture supernatant fluids. Both tests detected CCHF antigen at threshold values of approximately 2.5 log10 tissue culture infective doses per ml and were more sensitive than complement fixation, immunodiffusion, or immunofluorescence. In a comparative study on specimens from CCHF patients, virus was isolated from 38 of 49 sera and 23 of 28 patients. Antigen was detected in 20 of 49 sera (15 of 28 patients) by RPHA and in 29 of 49 sera (18 of 28 patients) by ELISA. Antigenemia was detected more frequently in fatal cases (9 of 11) than in nonfatal cases (9 of 17). Although the antigen detection assays offered a more rapid approach than infectivity assays for diagnosing CCHF, the latter test was more sensitive. The results suggest that RPHA and ELISA may be of use in rapid diagnosis of CCHF infection, particularly in severe cases, in which the danger of nosocomial spread is greatest.